According to a systematic review of clinical trials, migraine sufferers had higher blood prolactin levels than healthy controls. In order to better understand how the polypeptide hormone prolactin and its receptors affect headaches and migraine, researchers set out to evaluate clinical trials in a systematic manner.

For clinical trials examining prolactin signalling in migraine and headache, EMBASE and PubMed were explored using the terms head pain, headache, migraine, prolactin, hypoprolactinemia, macroprolactinemia, hyperprolactinemia, and trigeminal pain pathway. Overall, 841 publications were screened for population, intervention, comparison, outcome, and trial design by 2 reviewers independently. Studies with a nonexperimental technique were eliminated and limited to being written in English.

The qualitative and quantitative analysis comprised 19 clinical studies that matched the inclusion criteria. The serum prolactin levels were greater in migraineurs than in healthy controls, and prolactinomas (pituitary adenomas that secrete prolactin) were associated with higher rates of headache in otherwise healthy people and migraine episodes in migraineurs.

Prolactin and its receptors play a major role in the complex molecular interplay leading to migraine and headache. To further understand the role of prolactin in the onset of migraine attacks, additional randomized and placebo-controlled clinical trials focusing on prolactin signalling are required.